PROJECT SUMMARY/ABSTRACT Background. Recommendations for opioid agonist treatment (OAT) and against medically-supervised withdrawal (MSW) were based on early reports associating withdrawal with maternal relapse and fetal demise. While our recent systematic review did not support an association between MSW and fetal demise, relapse remains a significant concern with rates ranging from 0% to 100%. A retrospective report also suggests more delivery complications at delivery with MSW as compared to OAT. Neonatal outcomes after maternal MSW, however, are more positive, with retrospective reports suggesting MSW decreases the incidence of neonatal abstinence syndrome (NAS), reduces the amount of medication needed to treat NAS, and shortens neonatal length of hospital stay as compared to OAT. Given the literature?s mixed findings and methodological weaknesses, controlled prospective studies are needed. Study Design. The proposed study will be a four site, controlled, prospective, longitudinal, matched cohort study in which pregnant women with OUD who choose MSW at treatment entry (n=120) will be propensity- score matched with pregnant women with OUD who choose OAT at treatment entry (n=240) using maternal demographic, social, personal, and substance use history data collected at study entry. Women choosing MSW will undergo a 5-7 day withdrawal using buprenorphine; those choosing OAT will be inducted onto buprenorphine. All will receive comprehensive clinical care (obstetrical visits, group and individual counseling, case management, psychiatry services, and urine drug screening) and complete monthly research assessments with study staff. There will be a full assessment of maternal and neonatal health and well-being at birth, a minimum 4-day assessment of NAS, and a maternal postpartum assessment. Aim 1: (Exploratory) To determine the extent to which pregnant women with OUD seeking MSW differ from those seeking OAT in terms of demographic, social, personal, and substance use history characteristics. Aim 2: (Inferential) To examine the extent to which pregnant women with OUD seeking MSW differ from those seeking OAT in terms of maternal and neonatal outcomes. Aim 3. (Descriptive) To assess the ability of participant treatment entry characteristics to discriminate between (a) MSW participants who successfully complete their withdrawal protocol from MSW participants who do not; (b) MSW participants who successfully complete MSW and are opioid-negative at delivery from MSW participants who successfully complete their withdrawal protocol but discontinue treatment and are opioid-positive at delivery; and (c) participants who successfully complete MSW and are opioid-negative at delivery from participants who remain in OAT and are opioid-negative at delivery. Public Health Impact. This study will provide science- based evidence that addresses significant gaps in the treatment of OUD during pregnancy to be used by government, medical societies, providers and patients to inform treatment of mothers and neonates.